The identification of neurobiological markers associated with childhood status and persistence vs. remission of the attention deficit/hyperactivity disorder (ADHD) over development, and the translation of these markers into more effective diagnosis and intervention strategies are major priorities of NIMH. The persistence of ADHD into adulthood in many but not all afflicted children attests to the considerable variability in the remission of symptoms over development. However, evidence of cortical and subcortical structural anomalies associated with the persistence versus remission of ADHD is relatively limited, and not fully consistent. [Our group is in a unique position to test the neurobiological mechanisms associated with the childhood status and the developmental trajectories of ADHD]. We recently completed a 15-year longitudinal study of ADHD that recruited and clinically followed a large sample of children with ADHD into adulthood, as well as a well- matched sample of never ADHD controls that was recruited in adolescence and followed into adulthood. This large sample represents the diversity of outcomes characteristic of ADHD and was scanned with multi-modal neuroimaging in adulthood. Published results of our functional neuroimaging study support the distinction in neural mechanisms associated with the emergence and remission of ADHD. Young adults diagnosed with ADHD in childhood were marked by reduced regardless of adult outcome, while the remission of ADHD symptoms in adulthood was associated with enhanced cue-related thalamo-prefrontal functional connectivity. [However, the neuroanatomical evidence of this double-dissociation model of ADHD emergence and remission has not yet been investigated cue-related thalamus activation and functional connectivity with brainstem . By capitalizing on the availability of both neuroimaging and longitudinal clinical data from our recently completed study and utilizing advanced neuroimaging analysis and multivariate machine leaning techniques, this proposal aims to identify the neuroanatomical correlates of childhood status and remission of ADHD in young adults, and to link the anatomical evidence with the functional and longitudinal clinical evidence associated with persistent vs. remitted ADHD. The ultimate goal is to translate hypothesis-driven neuroanatomical correlates of adult outcome into clinically applicable biomarkers that can guide individualized interventions in youth with ADHD.] Our central hypotheses are that: (1) childhood ADHD is associated with thalamo-brainstem structural disconnectivity that endures into adulthood regardless of the developmental trajectory of the disorder; and (2) diminution of symptoms is related to optimal prefrontal development and its anatomical connectivity with other brain regions. The ultimate goal of this proposal is innovative and directly relevant to the NIMH mission, to translate hypothesis-driven neuroanatomical correlates of adult outcome into more clinically applicable biomarkers that can serve as targets for the development of interventions in youth with ADHD.